We have found that animals fed a diet containing cyclocreatine, an analogue of creatine; accumulate high concentrations of cyclocreatine-P (1-carboxymethyl-2-imino-3-phosphonoimidazolidine), an analogue of creatine phosphate, in heart, muscle, and brain. During postmortem ischemic hearts and muscles of animals fed cyclocreatine exhibit delayed onset of rigor mortis. Experiments performed during the first eight months of this grant have demonstrated that intracellular cyclocreatine-P can serve as a synthetic energy reservior for regeneration of ATP in both brain and skeletal muscles of mice after interruption of the blood circulation (ischemia). We have observed that glycogenolysis is suppressed during early stages of ischemia in skeletal muscles of mice fed cyclocreatine. Our data indicate that the rate of turnover of high energy phosphate is lowered in ischemic muscles and possibly brains of mice fed cyclocreatine. During the coming year we shall study the effects on postmortem rigor mortis of feeding animals diets containing two other anlogues of creatine systhesized in our laboratory. We shall also study the mechanisms by which cyclocreatine feeding suppresses glycogenolysis in skeletal muscle and compare this response with heart muscle. Interactions of certain hormones with these responses will be examined, noting in particular their effects on rigor mortis and glycogenolysis. Studies of the effects of cyclocreatine feeding on metabolism of other tissues will be continued, and related to the effects on heart metabolism. Heart failure has acute effects on brain metabolism, and utilization of brain cyclocreatine-P after circulation has stopped will be studied in both neurone and glial cell populations.